It is our purpose to study the mechanisms that control the plastic properties of the erythrocyte membrane, to detect abormalities of these properties that might relate to the pathogenesis of diseases, to explore that aspect of the erythrocyte storage lesion which relates to deterioration of membrane function, to begin an analysis of the biosynthesis of the erythrocyte plasma membrane, and to characterize the membrane associated enzymes in order to discover why some enzymes become associated with the membrane and others do not; and further, to determine if membrane association of an enzyme leads to alteration of its kinetic characteristics or to the acquisition of vectorial aspects of catalysis. The phenomenon of drug-induced membrane internalization in intact erythrocytes offers an opportunity to measure the interrelationships between bioenergetics and certain plastic or physical properties of the erythrocyte membrane. We propose to discover if drugs alter the interaction of Ca ions, Mg ions and ATP at the inner surface of the erythrocyte membrane. The role of energy metabolism in contributing to membrane properties will be investigated, and we will focus on the function of a membrane bound Ca ions, Mg ions -ATPase which appears to keep the Ca ions concentration at the inner surface of the membrane within very narrow limits. Having previously shown that there is defective drug induced internalization in hereditary spherocytosis, we will attempt to better define the abnormality. The mechanism by which sickle hemoglobin may interfere with membrane function will be studied. The kinetic and vectorial properties of two membrane associated glycolytic enzymes will be studied and we will look for possible perturbation of the function of these enzymes in those diseases where there appears to be denatured globin at the inner surface of the membrane. We will explore a hypothesis that the reason for intramedullary hemolysis relates to distrubed membrane function which may be consequent upon disturbed membrane biosynthesis. Studies on the biosynthesis of erythrocyte membranes will be performed in mouse and human.